RESUMEN
The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7-6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2-4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.
Asunto(s)
Antimaláricos/efectos adversos , Artemisininas/efectos adversos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Fluorenos/efectos adversos , Malaria Falciparum/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Combinación Arteméter y Lumefantrina , Artemisininas/administración & dosificación , Artemisininas/uso terapéutico , Artesunato , Atovacuona/administración & dosificación , Atovacuona/efectos adversos , Atovacuona/uso terapéutico , Audiometría , Niño , Colombia , Combinación de Medicamentos , Quimioterapia Combinada , Etanolaminas , Femenino , Fluorenos/administración & dosificación , Fluorenos/uso terapéutico , Humanos , Malaria Falciparum/parasitología , Masculino , Mefloquina/administración & dosificación , Mefloquina/efectos adversos , Mefloquina/uso terapéutico , Persona de Mediana Edad , Plasmodium falciparum/efectos de los fármacos , Proguanil/administración & dosificación , Proguanil/efectos adversos , Proguanil/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], P<0.0001). In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.
Asunto(s)
Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Naftoquinonas/uso terapéutico , Proguanil/uso terapéutico , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Adolescente , Adulto , Anciano , Animales , Antimaláricos/efectos adversos , Atovacuona , Cloroquina/efectos adversos , Combinación de Medicamentos , Farmacorresistencia Microbiana , Quimioterapia Combinada , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Naftoquinonas/efectos adversos , Perú , Proguanil/efectos adversos , Pirimetamina/efectos adversos , Sulfadoxina/efectos adversos , Resultado del TratamientoRESUMEN
The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.